#4151 POLYCYSTINS ARE REQUIRED FOR RENAL TUBULOINTERSTITIAL FIBROSIS

Abstract Background and Aims Renal fibrosis is the common pathway of various chronic kidney diseases progressing to end stage renal failure. Polycystin-1 (encoded by PKD1 gene) polycystin-2 PKD2 form a transmembrane complex function as stress sensor, which located in primary cilia. Polycystins are involved disease condition different organs. Mutation PKD genes causes autosomal dominant polycystic deletion polycystin attenuates heart injury induced cardiac fibrosis. The role polycystins tubulointerstitial currently unclear. Method Unilateral ureteral obstruction (UUO), unilateral ischemia-reperfusion (UIRI), aristolochic acid or folic mouse models were established for this study. Results Here we showed that up-regulated these three tightly correlated with expression collagen-I time dependent manner. Treatment triptolide inhibited pro-fibrotic markers UUO UIRI models. Moreover, siRNA vitro. Using Pkd2 conditional knockout mice, genetic reduced kidneys. was also fibrotic Pkd1 Furthermore, methyltransferase EZH2 positively Conditional attenuated anti-fibrotic responses Conclusion In conclusion, kidneys promote through up-regulation EZH2, suggesting cilia required